{"id":2152,"date":"2012-02-03T00:00:00","date_gmt":"2012-02-03T08:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/"},"modified":"2016-01-23T11:32:51","modified_gmt":"2016-01-23T19:32:51","slug":"discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/","title":{"rendered":"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases"},"content":{"rendered":"<p>LA JOLLA, CA\u2014One of the big mysteries in biology is why cells age. Now scientists at the Salk Institute for Biological Studies report that they have discovered a weakness in a component of brain cells that may explain how the aging process occurs in the brain.\n<\/p>\n<p>\nThe scientists discovered that certain proteins, called extremely long-lived proteins (ELLPs), which are found on the surface of the nucleus of neurons, have a remarkably long lifespan.\n<\/p>\n<p>\nWhile the lifespan of most proteins totals two days or less, the Salk<br \/>\nInstitute researchers identified ELLPs in the rat brain that were as old<br \/>\nas the organism, a finding they reported in <em>Wissenschaft<\/em>.\n<\/p>\n<p><iframe src=\"https:\/\/www.youtube.com\/embed\/MH80WhU3KTs?rel=0\" frameborder=\"0\" allowfullscreen><\/iframe><\/p>\n<p>\nThe Salk scientists are the first to discover an essential intracellular machine whose components include proteins of this age. Their results suggest the proteins last an entire lifetime, without being replaced.\n<\/p>\n<p>\nELLPs make up the transport channels on the surface of the nucleus; gates that control what materials enter and exit. Their long lifespan might be an advantage if not for the wear-and-tear that these proteins experience over time. Unlike other proteins in the body, ELLPs are not replaced when they incur aberrant chemical modifications and other damage.\n<\/p>\n<p>\nDamage to the ELLPs weakens the ability of the three-dimensional transport channels that are composed of these proteins to safeguard the cell&#8217;s nucleus from toxins, says <a href=\"\/de\/faculty\/hetzer.html\/\">Martin Hetzer<\/a>, a professor in Salk&#8217;s <a href=\"\/de\/faculty\/molecular_and_cell_biology_laboratory.html\/\">Labor f\u00fcr Molekular- und Zellbiologie<\/a>, who headed the research. These toxins may alter the cell&#8217;s DNA and thereby the activity of genes, resulting in cellular aging.\n<\/p>\n<p>\nFunded by the <a href=\"http:\/\/www.ellisonfoundation.org\/\">Ellison Medical Foundation<\/a> und die <a href=\"http:\/\/glennfoundation.org\/\">Glenn Stiftung f\u00fcr medizinische Forschung<\/a>, Hetzer&#8217;s research group is the only lab in the world that is investigating the role of these transport channels, called the nuclear pore complex (NPC), in the aging process.\n<\/p>\n<div class=\"imageCaption\"><img decoding=\"async\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2012\/01\/540_hetzer.jpg\" alt=\"extremely long-lived proteins\" width=\"300\"><\/p>\n<p>This microscope image shows extremely long-lived proteins, or ELLPs, glowing green on the outside of the nucleus of a rat brain cell. DNA inside the nucleus is pictured in blue.\n<\/p>\n<p>\nThe Salk scientists discovered that the ELLPs, which form channels through the wall of the nucleus, lasted for more than a year without being replaced. Deterioration of these proteins may allow toxins to enter the nucleus, resulting in cellular aging.\n<\/p>\n<p>Image: Courtesy of Brandon Toyama, Salk Institute for Biological Studies <\/p>\n<\/div>\n<p>\nPrevious studies have revealed that alterations in gene expression underlie the aging process. But, until the Hetzer lab&#8217;s discovery that mammals&#8217; NPCs possess an Achilles&#8217; heel that allows DNA-damaging toxins to enter the nucleus, the scientific community has had few solid clues about how these gene alterations occur.\n<\/p>\n<p>\n&#8220;The fundamental defining feature of aging is an overall decline in the functional capacity of various organs such as the heart and the brain,&#8221; says Hetzer.  &#8220;This decline results from deterioration of the homeostasis, or internal stability, within the constituent cells of those organs. Recent research in several laboratories has linked breakdown of protein homeostasis to declining cell function.&#8221;\n<\/p>\n<p>\nThe results that Hetzer and his team report today suggest that declining neuron function may originate in ELLPs that deteriorate as a result of damage over time.\n<\/p>\n<p>\n&#8220;Most cells, but not neurons, combat functional deterioration of their protein components through the process of protein turnover, in which the potentially impaired parts of the proteins are replaced with new functional copies,&#8221; says Hetzer.\n<\/p>\n<p>\n&#8220;Our results also suggest that nuclear pore deterioration might be a general aging mechanism leading to age-related defects in nuclear function, such as the loss of youthful gene expression programs,&#8221; he adds.\n<\/p>\n<p>\nThe findings may prove relevant to understanding the molecular origins of aging and such neurodegenerative disorders as Alzheimer&#8217;s disease and Parkinson&#8217;s disease.\n<\/p>\n<p>\nIn previous studies, Hetzer and his team discovered large filaments in the nuclei of neurons of old mice and rats, whose origins they traced to the cytoplasm. Such filaments have been linked to various neurological disorders including Parkinson&#8217;s disease. Whether the misplaced molecules are a cause, or a result, of the disease has not yet been determined.\n<\/p>\n<p>\nAlso in previous studies, Hetzer and his team documented age-dependent declines in the functioning of NPCs in the neurons of healthy aging rats, which are laboratory models of human biology.\n<\/p>\n<p>\nHetzer&#8217;s team includes his colleagues at the Salk Institute as well as John Yates III, a professor in the Department of Chemical Physiology of The Scripps Research Institute. The co-first authors on the study were Brandon H. Toyama, a postdoctoral researcher in Hetzer&#8217;s laboratory, and Jeffrey N. Savas, a postdoctoral researcher in Yates&#8217; laboratory.\n<\/p>\n<p>\nWhen Hetzer decided three years ago to investigate whether the NPC plays a role in initiating or contributing to the onset of aging and certain neurodegenerative diseases, some members of the scientific community warned him that such a study was too bold and would be difficult and expensive to conduct. But Hetzer was determined despite the warnings.\n<\/p>\n<p>\nHe adds that without foundation funding, the study would not have progressed to the point that its findings are published in a leading journal.<\/p>\n<p>\n<strong><br \/>\n\u00dcber das Salk Institute for Biological Studies:<br \/><\/strong><br \/>\nDas Salk Institute for Biological Studies ist eine der weltweit f\u00fchrenden Institutionen f\u00fcr Grundlagenforschung, an der international renommierte Fakult\u00e4tsmitglieder grundlegende Fragen der Biowissenschaften in einem einzigartigen, kollaborativen und kreativen Umfeld untersuchen. Mit dem Fokus auf Entdeckungen und die Ausbildung zuk\u00fcnftiger Forschergenerationen leisten Salk-Wissenschaftler bahnbrechende Beitr\u00e4ge zu unserem Verst\u00e4ndnis von Krebs, Alterung, Alzheimer, Diabetes und Infektionskrankheiten durch die Untersuchung von Neurowissenschaften, Genetik, Zell- und Pflanzenbiologie sowie verwandten Disziplinen.\n<\/p>\n<p>\nDie Leistungen der Fakult\u00e4t wurden mit zahlreichen Auszeichnungen gew\u00fcrdigt, darunter Nobelpreise und Mitgliedschaften in der National Academy of Sciences. Das 1960 vom Polio-Impfstoff-Pionier Dr. Jonas Salk gegr\u00fcndete Institut ist eine unabh\u00e4ngige gemeinn\u00fctzige Organisation und ein architektonisches Wahrzeichen.<\/p>\n<p><strong>For more information:<\/strong><br \/>\n<em>Wissenschaft<\/em><br \/>\nAuthors: Jeffrey N. Savas, Brandon H. Toyama, Tao Xu, John R. Yates and Martin W. Hetzer<br \/>\n<a href=\"http:\/\/www.sciencemag.org\/content\/early\/2012\/02\/01\/science.1217421.abstract?sid=6b60fd73-8b71-4ae0-90d5-a183a69d40d0\">Extremely Long-Lived Nuclear Pore Proteins in the Rat Brain<\/a><\/p>","protected":false},"featured_media":0,"template":"","faculty":[86],"disease-research":[127,146,124,162],"class_list":["post-2152","disclosure","type-disclosure","status-publish","hentry","faculty-martin-hetzer","disease-research-alzheimers-disease","disease-research-aging-and-regenerative-medicine","disease-research-neuroscience-and-neurological-disorders","disease-research-parkinsons-disease"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA, CA\u2014One of the big mysteries in biology is why cells age. Now scientists at the Salk Institute for Biological Studies report that they have discovered a weakness in a component of brain cells that may explain how the aging process occurs in the brain.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/de\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2016-01-23T19:32:51+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"628\" \/>\n\t<meta property=\"og:image:height\" content=\"329\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/\",\"name\":\"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2012\\\/01\\\/540_hetzer.jpg\",\"datePublished\":\"2012-02-03T08:00:00+00:00\",\"dateModified\":\"2016-01-23T19:32:51+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/#breadcrumb\"},\"inLanguage\":\"de-DE\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"de-DE\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2012\\\/01\\\/540_hetzer.jpg\",\"contentUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2012\\\/01\\\/540_hetzer.jpg\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"de-DE\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"de-DE\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/de\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/","og_locale":"de_DE","og_type":"article","og_title":"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases - Salk Institute for Biological Studies","og_description":"LA JOLLA, CA\u2014One of the big mysteries in biology is why cells age. Now scientists at the Salk Institute for Biological Studies report that they have discovered a weakness in a component of brain cells that may explain how the aging process occurs in the brain.","og_url":"https:\/\/www.salk.edu\/de\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/","og_site_name":"Salk Institute for Biological Studies","article_modified_time":"2016-01-23T19:32:51+00:00","og_image":[{"width":628,"height":329,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"5 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/","url":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/","name":"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/#primaryimage"},"thumbnailUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2012\/01\/540_hetzer.jpg","datePublished":"2012-02-03T08:00:00+00:00","dateModified":"2016-01-23T19:32:51+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/#breadcrumb"},"inLanguage":"de-DE","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/"]}]},{"@type":"ImageObject","inLanguage":"de-DE","@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/#primaryimage","url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2012\/01\/540_hetzer.jpg","contentUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2012\/01\/540_hetzer.jpg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/discovery-of-extremely-long-lived-proteins-may-provide-insight-into-cell-aging-and-neurodegenerative-diseases\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Discovery of extremely long-lived proteins may provide insight into cell aging and neurodegenerative diseases"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"Salk-Institut f\u00fcr biologische Studien","description":"Die Macht der Wissenschaft","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"de-DE"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"Salk-Institut f\u00fcr biologische Studien","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"de-DE","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"paper_url":"http:\/\/www.sciencemag.org\/content\/early\/2012\/02\/01\/science.1217421.abstract?sid=6b60fd73-8b71-4ae0-90d5-a183a69d40d0","journal_title":"Science","paper_author_list":"Jeffrey N. Savas, Brandon H. Toyama, Tao Xu, John R. Yates and Martin W. Hetzer","paper_title":"Extremely Long-Lived Nuclear Pore Proteins in the Rat Brain","subhead":"Salk researchers find that the adult brain contains proteins that last a lifetime","home_photo":"2012\/540_HetzerHeadshot.jpg","listing_photo":"540.jpg","gallery":false,"legacy_boilerplate":[]},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/2152","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":0,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/2152\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/media?parent=2152"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/faculty?post=2152"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disease-research?post=2152"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}